The ability to control the active concentration of neurotransmitters in a spatially and temporally precise manner has revolutionized the study of the central nervous system. In particular, caged glutamate has emerged as a tool for the dissection of both neural circuitry and the fast kinetic events of channel activation. Upon the irreversible photochemical cleavage of a protecting group, released glutamate is free to bind ionotropic glutamate receptors (iGluRs), the major mediators of excitatory information transfer in the central nervous system.
Photochromic ligands provide another opportunity for the control of neural excitability. First reported in the late 1960's in the form of a photoisomerizable inactivator of chymotrypsin, photochromic ligands control the function of proteins through a reversible change in shape and/or polarity of an integral bistable photoswitch. In the case of photochromic agonists, one configuration functions as an activating ligand, while the other configuration is, ideally, inert toward the system of study. Photochromic nicotinic acetylcholine receptor agonists, enzyme inhibitors, and regulatory peptides have been reported; however, their benefits have been tempered by the difficulty of achieving perfect on/off activity between states.
Literture
Kaufman et al. (1968) Science 162:1487-1489; Bartels et al. (1971) Proc. Natl. Acad. Sci. U.S.A. 68:1820-1823; Fujita et al. (2006) Biochemistry 45:6581-6586; Caamano et al. (2000) Angew. Chem., Int. Ed. Engl. 39:3104-3107; Mayer and Heckel (2006) Angew. Chem., Int. Ed. Engl. 45:4900-4921; Givens et al. (1998) In Methods in Enzymology, Marriott, G., Ed. Academic Press, New York, 291:1-29; Volgraf et al. (2006) Nature Chem. Biol. 2:47-52; U.S. Patent Publication No. 2007/0128662; Lester et al. J. Gen. Physiol. 75, 207-232 (1980); Banghart et al. Nature Neurosci. 7, 1381-1386 (2004).